Macrolides
Examples
- Erythromycin
- Clarithromycin
- Azithromycin
Indications
- Very similar to penicillins and often used in penicillin allergy
- Also useful against atypical pneumonias and chlamydia
- Can also be one of the antibiotics used in the eradication of H.pylori
Contraindications
Contraindications
- Allergic reaction to macrolides
- Severe liver disease
- Predisposition to QT interval prolongation
- Reduced renal function
- Myasthenia Gravis
Mechanism
The macrolides inhibit bacterial ribosomal protein synthesis, interfering with protein translocation by binding the 50S subunit. The macrolides are bacteriostatic but, depending on the concentration and micro-organism, can have bacteriocidal action.
Administration
- Eryhtromycin - Oral, I.V.
- Clarithromycin - Oral, IV.
- Azithromycin - Oral
Adverse Reactions
- Nausea and vomiting, abdominal discomfort and diarrhoea are the most common side effects (more common with erythromycin as this specifically stimulates motilin receptors in the gut)
- Hepatotoxicity (including cholestatic jaundice) and rash occur less frequently
- Intravenous infusion may cause local tenderness and phlebitis
- Can prolong the QT interval
Interactions
- The macrolides bind the same 50S subunit of the bacterial ribosome as clindamycin and chloramphenicol and may compete if given concurrently
- Should be avoided in combination with other drugs that cause prolonged QT
- Clarithromycin and erythromycin inhibit liver P450 enzymes - particularly problematic with warfarin, anti-convulsants, and theophylline. Always consult the BNF prior to prescribing
- Clarithromycin interacts with statins, particularly simvastatin. If the patient is prescribed a course of clarithromycin, then it is recommended that they withhold their simvastatin until after the course of clarithromycin is completed.
- Clarithromycin can increase the exposure to some opioids (oxycodone, fentanyl etc). Opioid dose may require some adjustment.
- Clarithromycin and other macrolides can inhibit the P-Glycoprotein efflux transporter. This can affect drugs that act as substrates for this transporter. Examples include digoxin and colchicine. This can result in increased drug serum concentrations for these medicines.
Education
Patients should be advised to complete the prescribed course of antibiotic therapy.
Pharmacokinetics
The macrolides are primarily administered orally, they diffuse well into all tissues but do not cross the blood brain barrier and penetration into the synovial fluid is poor, so these drugs are not useful in CNS or joint infections.
Their effects on cytochrome p450 enzyme can affect other drugs.
The major route of elimination is in the bile.
Their effects on cytochrome p450 enzyme can affect other drugs.
The major route of elimination is in the bile.
